Bone density in relation to alcohol intake among men and women in the United States

Summary Studies of postmenopausal women have shown a positive association between BMD and alcohol intake. We found that BMD was higher in men, and possibly postmenopausal women, who drank alcohol compared with those who abstained. Drinking alcohol, but not binge drinking, may benefit bone health of men and postmenopausal women. Introduction Osteoporotic fractures account for over 2.5 million physician visits annually for persons ages ≥45 years in the United States. Studies of postmenopausal women show a positive association between bone mineral density (BMD) and alcohol intake, but for men and premenopausal women, the bone–alcohol relationship remains unclear. We examined the association between total hip (TH) and femoral neck (FN) BMD and alcohol intake of men and pre- and postmenopausal women. Methods We conducted multiple regression analyses using data from 13,512 persons ages ≥20 years from the Third National Health and Nutrition Examination Survey, 1988–1994. Alcohol intake and binge drinking were measured by questionnaire and hip BMD by dual energy X-ray absorptiometry (DXA). Results Accounting for covariates, TH BMD was higher in men (n = 6,868) who had 5–29 (+2.1%, p < 0.01) and >29 drinking occasions/month (+1.7%, p < 0.05) than men who abstained. BMD of premenopausal women (n = 4,136) who drank alcohol did not differ from those who abstained. FN BMD was 3.8% higher in postmenopausal women (n = 2,043) who had >29 drinking occasions/month than those who abstained (p = 0.06). Binge drinking was not associated with BMD of men or women. Conclusions Drinking alcohol, but not binge drinking, appears to be beneficial to bone health of men and possibly postmenopausal women.     

Physical training preserves bone mineral density in postmenopausal women with forearm fractures and low bone mineral density

Summary One hundred and twelve postmenopausal women with low bone mineral density (BMD) and forearm fractures were randomized to physical training or control group. After one year the total hip BMD was significantly higher in the women in the physical training group. The results indicate a positive effect of physical training on BMD in postmenopausal women with low BMD. Introduction The fivefold increase in hip fracture incidence since 1950 in Sweden may partially be due to an increasingly sedentary lifestyle. Our hypothesis was that physical training can prevent bone loss in postmenopausal women. Methods One hundred and twelve postmenopausal women 45 to 65 years with forearm fractures and T-scores from −1.0 to −3.0 were randomized to either a physical training or control group. Training included three fast 30-minute walks and two sessions of one-hour training per week. Bone mineral density (BMD) was measured in the hip and the lumbar spine at baseline and after one year. Results A per protocol analysis was performed, including 48 subjects in the training group and 44 subjects in the control group. The total hip BMD increased in the training group +0.005 g/cm2 (±0.018), +0.58%, while it decreased −0.003 g/cm2 (±0.019), −0.36%, (p = 0.041) in the control group. No significant effects of physical training were seen in the lumbar spine. A sensitivity intention to treat analysis, including all randomized subjects, showed no significant effect of physical training on BMD at any site. Conclusions The results indicate a small but positive effect of physical exercise on hip BMD in postmenopausal women with low BMD.     

Forearm Bone Mineral Densitometry Cannot be Used to Monitor Response to Alendronate Therapy in Postmenopausal Women

Alendronate significantly increases bone mass and reduces hip and spine fractures in postmenopausal women. To determine whether forearm densitometry could be used to monitor the efficacy of alendronate, we examined changes in bone mineral density (BMD) at the forearm (one-third distal, mid-distal, ultradistal radius) versus changes at the hip (femoral neck, total hip) and spine (posteroanterior and lateral) in a double-masked, randomized, placebo-controlled clinical trial of 120 elderly women (mean age 70 ± 4 years) treated with alendronate for 2.5 years. We found that among women in the treatment group, BMD increased by 4.0–12.2% at the hip and spine sites (all p<0.001), whereas BMD increased only nominally at the one-third distal radius (1.3%, p<0.001) and mid-radius (0.8%, p<0.05), and remained stable at the ultradistal radius. At baseline, forearm BMD correlated with that of the hip (r= 0.55–0.64, p<0.001), femoral neck (r= 0.54–0.61, p<0.001) and posteroanterior spine (r= 0.56–0.63, p<0.001). Changes in radial BMD after 1 year of therapy were not correlated with changes in hip and spine BMD after 2.5 years of therapy. In contrast, short-term changes in total hip and spine BMD were generally positively associated with long-term changes in total hip, femoral neck and spine BMD (r= 0.30–0.71, p<0.05). Furthermore, long-term BMD changes at the forearm did not correlate with long-term hip and spine BMD changes, in contrast to the moderate correlations seen between spine and hip BMD at 2.5 years (r= 0.38–0.45, p<0.01). We conclude that neither short- nor long-term changes in forearm BMD predict long-term changes in overall BMD for elderly women on alendronate therapy, suggesting that measurements of clinically relevant central sites (hip and spine) are necessary to assess therapeutic efficacy. Received: 18 February 1999 / Accepted: 20 May 1999     

Changes in soft tissue composition are the primary predictors of 4-year bone mineral density changes in postmenopausal women

Summary  Changes in body weight influence bone mineral density, but the role of body composition is not clear in postmenopausal women. Body weight and soft tissue composition predicted bone changes independent of calcium supplementation and exercise frequency, indicating that soft tissue composition should be measured in clinical trials. Introduction  The purpose of this study was to examine the relationship between changes in body weight and composition and changes in 4-year bone mineral density (BMD) after accounting for age, 4-year exercise frequency (EX), and 4-year calcium supplement intake (CA) in postmenopausal women with and without hormone therapy (HT). Methods  Postmenopausal women (aged 40–65 years) either using HT (for 1–3.9 years) or not using HT (for ≥1 year) were recruited to the study. EX and CA was monitored throughout the study and 167 women completed 4 years. BMD and soft tissue composition measurements were made using dual-energy X-ray absorptiometry. Regression was used to predict 4-year BMD changes from EX, CA, age, baseline and 4-year changes in body weight and composition. HT users (n = 115, 55.3 ± 4.3 years) and non-users (n = 52, 57.5 ± 4.7 years) were analyzed separately. Results  The models predicting regional BMD changes that included soft tissue composition changes explained the most variation compared with those with body weight or EX and CA alone. Larger amounts of variation in BMD changes were explained in the no HT group. Conclusion  Body composition changes are important positive predictors of BMD changes independent of EX and CA supplementation, but their contribution varies according to bone site and with HT use.     

Quantitative Ultrasound and Symptomatic Vertebral Fracture Risk in Chinese Women

Quantitative ultrasound (QUS) is emerging as a simple, inexpensive and noninvasive method for assessing bone quality and assessing fracture risk. We assessed the usefulness of a contact calcaneal ultrasonometer by studying normal premenopausal women (group I, n= 53), normal postmenopausal women (group II, n= 198), and osteoporotic women without (group III, n= 141) and with vertebral fractures (group IV, n= 53). The osteoporotic subjects had a T-score of the spine or hip neck bone mineral density (BMD) <−2.5 based on the local Chinese peak young mean values. When compared with postmenopausal controls, mean broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI) were 26%, 2.1% and 25% lower in women with vertebral fractures (p all <0.005). The correlation coefficients between QUS parameters and BMD of the spine and hip ranged between 0.4 and 0.5. The ability of the QUS to discriminate between patients groups was determined based on the mean value of normal premenopausal women in group I. The mean T-score for women with fractures was −2.87 ± 1.02 for BUA, −2.54 ± 0.79 for SOS, −3.17 ± 0.70 for QUI, −2.65 ± 0.86 for L2–4 BMD and −2.53 ± 0.66 for hip neck BMD. After adjustment for age and body mass index, the odds ratio of vertebral fracture was 1.71 (95% CI 1.2–2.6) for each 1 SD reduction in BUA, 2.72 (1.3–5.3) for SOS, 2.58 (1.4–4.6) for QUI, 2.33 (1.6–3.3) for L2–4 BMD, 2.09 (1.37–3.20) for femoral neck BMD and 1.88 (1.34–2.92) for total hip BMD. The association between the QUS parameters and vertebral fracture risk persisted even adjustment for BMD. The area under the receiver operating characteristic curve for BUA for vertebral fracture was 0.92, for SOS, QUI, L2–4 BMD and femoral neck BMD was 0.95, and for total hip was 0.91. Received: 7 January 1999 / Accepted: 18 May 1999     

Effects of combined whole-body vibration and resistance training on muscular strength and bone metabolism in postmenopausal women

Whole-body vibration (WBV) has been shown to be osteogenic in animal models; however, its application in humans is not clear. The purpose of this study was to examine the effects of an 8-month program involving WBV plus resistance training on bone mineral density (BMD) and bone metabolism in older postmenopausal women. Fifty-five estrogen-deficient postmenopausal women were assigned to a resistance training group (R, n = 22), a WBV plus resistance training group (WBVR, n = 21), or a control group (CON, n = 12). R and WBVR performed upper and lower body resistance exercises 3 days/week at 80% 1 Repetition Maximum (1RM). WBVR received vibration (30–40 Hz, 2–2.8g) in three different positions preceding the resistance exercises. Daily calcium intake, bone markers (Bone alkaline phosphatase (Bone ALP); C-terminal telopeptide of Type I collagen (CTX), and BMD of the spine, dual femur, forearm, and total body (DXA) were measured at baseline and after the intervention. At baseline, there were no significant group differences in strength, BMD, or bone marker variables. After 8 months of R or WBVR, there were no significant group or time effects in Bone ALP, CTX, or total body, spine, left hip or right trochanter BMD. However, right total hip and right femoral neck BMD significantly (p < 0.05) decreased in all groups. A group × time interaction (p < 0.05) was detected at radius 33% BMD site, with CON slightly increasing, and WBVR slightly decreasing. R and WBVR significantly (p < 0.05) increased 1RM strength for all exercises, while CON generally maintained strength. WBVR had significantly (p < 0.05) greater percent increases in muscular strength than R at 4 months for lat pull down, seated row, hip abduction and hip adduction and at 8 months for lat pull down, hip abduction and hip adduction. Bone metabolism in postmenopausal women was not affected by resistance training either with or without WBV. In contrast, the addition of WBV augmented the positive effects of resistance training on muscular strength in these older women.     

Low bone mass is associated with carotid atherosclerosis in postmenopausal women: The Japanese Population-based Osteoporosis (JPOS) Cohort Study

Summary  We analyzed 609 women belonging to the JPOS study in a 10-year follow-up survey, to examine the association of osteoporosis with atherosclerosis. Osteoporosis or prevalent vertebral fracture at baseline was associated with increased intima-media thickness of the carotid bifurcation in postmenopausal women, adjusted for age, BMI, and other variables at baseline. Introduction  Whether low bone mass predicts increased carotid atherosclerosis has not been fully investigated. Methods  In 2006, we conducted a 10-year follow-up survey of 1,040 women (follow-up rate: 68.6%). We analyzed 609 women ≥50 years old in 2006 without a history of cardiovascular or connective tissue diseases at baseline. BMD and evaluation of vertebral fracture at baseline were used. The intima-media thickness of carotid bifurcation (BIF-IMT) was measured by B-mode ultrasonography in 2006. Results  Adjusted BIF-IMT values of subjects with spine T-score ≥-1, between-2.5 and -1, and <-2.5 or prevalent vertebral fracture were 1.19 mm, 1.34 mm, 1.57 mm, respectively, in women with less than 10 years since menopause (YSM) (n = 159), 1.30 mm, 1.32 mm, 1.53 mm, in women with YSM ≥10 without a history of hypertension at baseline (n = 144) (both with p < 0.05 for linear trend). Those values among no versus prevalent vertebral fracture in women with YSM ≥10 were 1.40 mm, 1.66 mm with p < 0.05 (n = 202). Those associations were independent of age, BMI, total cholesterol, smoking and drinking habits, history of diabetes mellitus, and hypertension (for women with YSM < 10) at baseline. Conclusion  Osteoporosis including prevalent vertebral fracture may be associated with carotid atherosclerosis in the first 10 years of postmenopausal women.     

Effect of exercise training and detraining on bone mineral density in postmenopausal women with osteoporosis

We examined the effect of exercise training and detraining on bone mineral density (BMD) in postmenopausal women with osteoporosis. Thirty-five postmenopausal women with osteoporosis, aged 53–77 years, were randomly assigned to three groups: a control group (n = 20), a 2-year exercise training group (n = 8), and an 1-year exercise training plus 1-year detraining group (n = 7). Exercise training consisted of daily brisk walking and gymnastic training. Calcium lactate, 2.0 g, and 1α-hydroxyvitamin D₃, 1 μg were supplied daily to all subjects. No significant differences in initial lumbar BMD, measured by dual-energy X-ray absorptiometry (DXA) were found among the three groups. The mean percent change in BMD compared with the baseline was significantly higher at 1 and 2 years in the exercise training group and at 1 year in the detraining group than in the control group, and did not differ significantly at 2 years between the detraining and control groups. These findings indicate that our exercise training program led to a significant increase in lumbar BMD in postmenopausal women with osteoporosis compared with the control, but that the BMD reverted toward a level that was not significantly different from the control with detraining. Continued exercise training is needed to maintain the bone mass gained through exercise training. Received: May 6, 2000 / Accepted: October 6, 2000     

Vitamin D insufficiency does not affect response of bone mineral density to alendronate

Summary  We investigated whether osteoporosis therapy with alendronate in postmenopausal patients is equally effective in patients who are vitamin D insufficient as in those who are vitamin D sufficient. We found that vitamin D insufficiency is common among patients with low bone density but that vitamin D insufficiency did not impair response to alendronate. Introduction  Treatment of vitamin D deficiency leads to significant improvements in bone mineral density (BMD); however, whether insufficiency affects BMD’s response to bisphosphonate therapy is unknown. Methods  To determine whether vitamin D insufficiency at initiation of alendronate therapy for low BMD affects treatment efficacy, we used data from 1,000 postmenopausal women randomly selected from the vertebral fracture arm (n = 2,027) of the placebo-controlled Fracture Intervention Trial of alendronate. Participants were randomly assigned to placebo (50%) or alendronate therapy and most (83%) to calcium (500 mg/day) and cholecalciferol (250 IU/day). We measured serum 25-hydroxy vitamin D (25OHD) at enrollment, then categorized baseline vitamin D status according to 25OHD concentration ( ≤ 10 ng/ml = deficient; >10 but ≤ 30 ng/ml = insufficient; >30 ng/ml = sufficient) and used linear regression to compare the effects of alendronate treatment among these categories. Results and conclusion  At baseline, participants were vitamin D sufficient (14%), insufficient (83%), and deficient (2%). We found that BMD response to therapy at total hip or spine did not vary by vitamin D status at baseline (p for heterogeneity = 0.6). We determined that vitamin D insufficiency is common among participants with low BMD. However, vitamin D status at initiation of therapy does not affect BMD’s response to alendronate, when it is coadministered with cholecalciferol and calcium. Scholar’s Grant from the National Osteoporosis Foundation (to D.M.A) and National Institutes of Health grant K23 RR020343 (to D.M.A).     

Addition of Aerobic Exercise to a Weight Loss Program Increases BMD,with an Associated Reduction in Inflammation in Overweight Postmenopausal Women

Increased inflammation and weight loss are associated with a reduction in bone mineral density (BMD). Aerobic exercise may minimize the loss of bone and weight loss may contribute to a decrease in cytokines. We tested the hypothesis that aerobic exercise in combination with a weight loss program would decrease circulating concentrations of inflammatory markers, thus mediating changes in BMD. This was a nonrandomized controlled trial. Eighty-six overweight and obese postmenopausal women (50–70 years of age; BMI, 25–40 kg/m²) participated in a weight loss (WL; n = 40) or weight loss plus walking (WL + AEX; n = 46) program. Outcome measures included BMD and bone mineral content of the femoral neck and lumbar spine measured by dual energy X-ray absorptiometry, interleukin-6, tumor necrosis factor-α, soluble receptors of IL-6, and TNF-α (sTNFR1 and sTNFR2; receptors in a subset of the population), VO₂ max, fat mass, and lean mass. Weight decreased in the WL (p < 0.001) and WL + AEX (p < 0.001) groups. VO₂ max increased (p < 0.001) after WL + AEX. There was a 2% increase in femoral neck BMD in the WL + AEX group (p = 0.001), which was significantly different from the WL group. The change in sTNFR1 was significantly associated with the change in femoral neck BMD (p < 0.05). The change in VO₂ max was an independent predictor of the change in femoral neck BMD. Our findings suggest that the addition of aerobic exercise is recommended to decrease inflammation and increase BMD during weight loss in overweight postmenopausal women.     

Occupational Activity and Bone Mineral Density in Postmenopausal Women in England

Few studies have assessed the relationship between occupational activity and bone mineral density (BMD), although two case–control studies have reported a protective effect of occupational activity on hip fracture. In the present study 580 postmenopausal women aged 45–61 years completed a risk factor questionnaire including a detailed occupational history. For each job, hours spent sitting, standing, walking, lifting and carrying were recorded; these measures, evaluated at ages 20, 30, 40 years, in the current job and over the working lifetime, were used in the analysis. BMD was measured with dual-energy X-ray absorptiometry, and measurements at five sites were used in a multiple regression analysis adjusting for potential confounding variables. There was a significant negative association between sitting at age 20 years and BMD at the radius (p= 0.037), with negative relationships of borderline significance at the anteroposterior spine (p = 0.091) and whole body (p= 0.078). There were significant positive associations between standing at age 30 years and BMD at all five sites (p<0.05), but no significant linear associations for standing at ages 20 and 40 years. No significant associations were found for lifetime or current occupational measures of sitting, standing, walking and lifting or carrying. The lack of consistency of these significant findings suggests that they may have occurred by chance, and that occupational activity has little if any effect on BMD in postmenopausal women. Received: 12 March 1999 / Accepted: 17 September 1999     

Effect of antioxidants combined to resistance training on BMD in elderly women: a pilot study

Summary  We determined the effect of antioxidants and resistance training on bone mineral density of postmenopausal women. After 6 months, we observed a significant decrease in the lumbar spine BMD of the placebo group while other groups remained stable. Antioxidants may offer protection against bone loss such as resistance training. Introduction  The purpose of this pilot study was to determine the effects of antioxidant supplements combined to resistance training on bone mineral density (BMD) in healthy elderly women. Methods  Thirty-four postmenopausal women (66.1 ± 3.3 years) were randomized in four groups (placebo, n = 7; antioxidants, n = 8; exercise and placebo, n = 11; and exercise and antioxidants, n = 8). The 6-month intervention consisted in antioxidant supplements (600 mg vitamin E and 1,000 mg vitamin C daily) or resistance exercise (3×/week). Femoral neck and lumbar spine BMD (DXA) and dietary intakes (3-day food record) were measured before and after the intervention. A repeated measure ANOVA and non-parametric Mann–Whitney U tests were used. Results  We observed a significant decrease in the placebo group for lumbar spine BMD (pre, 1.01 ± 0.17 g/cm²; post, 1.00 ± 0.16 g/cm²; P < 0.05 respectively) while it remained stable in all other groups. No changes were observed for femoral neck BMD. Conclusions  Antioxidant vitamins may offer some protection against bone loss in the same extent as resistance exercise although combining both does not seem to produce additional effects. Our results suggest to further investigate the impact of antioxidant supplements on the prevention of osteoporosis.     

The relationship between endogenous estrogen,sex hormone-binding globulin,and bone loss in female residents of a rural Japanese community: the Taiji Study

 The aim of this study was to clarify the relationship between endogenous estrogen, sex hormone-binding globulin (SHBG), and bone loss in pre-, peri-, and postmenopausal female residents of Taiji, a rural Japanese community. From a list of inhabitants aged 40 to 79 years, 200 participants—50 women in each of four age decades—were randomly selected, and baseline bone mineral density (BMD) at the lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry in 1993. Total estradiol (total E2) and SHBG were measured, and SHBG-unbound E2 (UBE2) was calculated using SHBG and the percent SHBG-unbound fraction ratio. BMD was measured again 3 years later, in 1996. Participants with ovariectomy or hysterectomy were excluded, and the remaining participants were categorized into four groups: premenopausal (n= 38), perimenopausal (n= 14), postmenopausal group 1 (5 years or less since menopause; n= 18), and postmenopausal group 2 (6 years or more since menopause; n= 74). The mean value of total E2 was highest in the premenopausal group (49.1 pg/ml), followed by the perimenopausal group (26.4 pg/ml), and the postmenopausal groups (0.83 pg/ml in postmenopausal group 1 and 0.96 pg/ml in postmenopausal group 2). The means for UBE2 showed the same pattern across the groups. After the multiple regression analysis of BMD at follow-up and endogenous estrogens, in premenopausal women, there were no significant associations between BMD at follow-up and serum total E2 and UBE2. In perimenopausal women, however, serum total E2 and UBE2 were significantly correlated with trochanteric BMD at follow-up (P < 0.05); and in postmenopausal group 2, they were significantly correlated with lumbar spine and Ward's triangle BMD at follow-up (P < 0.001 at lumbar spine, P < 0.05 at Ward's triangle). Concerning the association between BMD at follow-up and SHBG, in the premenopausal group, serum levels of SHBG were negatively correlated with BMD at the femoral neck (P < 0.05). In regard to partial regression coefficients for the change rates of BMD over 3 years and serum estrogens and SHBG concentrations, in perimenopausal women, UBE2 was correlated with the change rate of BMD at Ward's triangle (P < 0.05), and in postmenopausal group 1, serum levels of SHBG were significantly negatively related to change in BMD at the trochanter (P < 0.01). No other relationships with change in BMD were observed at any sites. These findings suggest that serum E2, UBE2, and SHBG levels differentially predict BMD levels in groups of differing menstrual status. It would, however, be difficult to predict bone loss in middle-aged and elderly Japanese women over a 3-year period using these indices alone. Received: November 29, 2001 / Accepted: February 28, 2002     

Competitive physical activity early in life is associated with bone mineral density in elderly Swedish men

Summary  In this population-based study of 75-year-old men (n = 498), we investigated the association between physical activity (PA) early in life and present bone mineral density (BMD). We demonstrate that a high frequency of competitive sports early in life is associated with BMD at several bone sites, indicating that increases in BMD following PA are preserved longer than previously believed. Introduction  Physical activity (PA) increases bone mineral density (BMD) during growth. It is unclear if the positive effects remain at old age. In this study, we aimed to determine if PA early in life was associated with BMD in elderly men. Methods  In this population-based study, 498 men, 75.2 ± 3.3 (mean±SD) years old, were included. BMD was assessed using DXA. Data concerning lifetime PA, including both competitive (CS) and recreational sports (RS), and occupational physical load (OPL), were collected at interview. Results  Subjects in the highest frequency group of CS in the early period (10–35 years), had higher BMD at the total body (4.2%, p < 0.01), total hip (7.0%, p < 0.01), trochanter (8.7%, p < 0.01), and lumbar spine (7.9%, p < 0.01), than subjects not involved in CS. A stepwise linear regression model showed that frequency of CS in the early period independently positively predicted present BMD at the total body (β = 0.12, p < 0.01), total hip (β = 0.11, p < 0.01), trochanter (β = 0.12, p < 0.01), and lumbar spine (β = 0.11, p = 0.01). Conclusions  We demonstrate that PA in CS early in life is associated with BMD in 75-year-old Swedish men, indicating that increases in BMD following PA are preserved longer than previously believed. This study was supported by the Swedish Research Council, the ALF/LUA grant from the Sahlgrenska University Hospital, and the Hjalmar Svensson Foundation.     

Physical training increases osteoprotegerin in postmenopausal women

The purpose of this study was to explore whether mechanical loading by exercise over a 1–year period in postmenopausal women had an effect on the receptor activator for nuclear factor kappa B ligand/osteoprotegerin (RANKL/OPG) system or the levels of the Wnt-signaling antagonist sclerostin. A total of 112 postmenopausal were randomized to either sedentary life (controls) or physical activity (training group). Ninety-two women fulfilled the study protocol. The training program consisted of three fast 30-min walks and one or two 1-h aerobic training sessions per week. The effect on the bone mineral density of the hip assessed with dual X-ray absorptiometry was positive as reported earlier. Blood samples were taken from participants at baseline and after 1 year and serum levels of OPG, RANKL and sclerostin were quantified together with the bone metabolism markers C-terminal telopeptide of collagen type I (CTX) and bone-specific alkaline phosphatase (BALP). The results were analyzed using an analysis of covariance model using baseline values as the covariate. The training group displayed a clear mean increase of OPG +7.55 pg/ml compared to controls (p = 0.007). The mean changes for RANKL +0.19 pg/ml (square-root transformed data) and sclerostin +0.62 pmol/l were non-significant (p = 0.13 and p = 0.34). The changes in bone turnover markers CTX and BALP showed a tendency to decrease in the training group versus controls but the changes were small and non-significant. Although our study is limited in number of participating women, we have been able to show an OPG-associated, and RANKL- and sclerostin-independent, training-induced inhibition of postmenopausal bone loss.     

Randomized Trial of Alendronate Plus Vitamin D<Subscript>3</Subscript> Versus Standard Care in Osteoporotic Postmenopausal Women with Vitamin D Insufficiency

Vitamin D insufficiency is common in patients with osteoporosis. We conducted a randomized trial comparing alendronate 70 mg combined with vitamin D₃ 5,600 IU in a single tablet (ALN/D5600, n = 257) with standard care chosen by the patients’ personal physicians (n = 258) in patients with postmenopausal osteoporosis (BMD T score ≤2.5 or ≤1.5 and a prior fragility fracture) who had vitamin D insufficiency (serum 25[OH]D values 8–20 ng/ml) and who were at risk of falls. Virtually all patients randomized to standard care received bisphosphonate therapy, and in approximately 70% of cases this was combined with vitamin D supplements. However, only 24% took ≥800 IU/day of supplemental vitamin D. At 6 months the proportion of patients with vitamin D insufficiency was 8.6% in the ALN/D5600 group compared with 31.0% in the standard care group (P < 0.001). Those in the ALN/D5600 group also had a greater reduction in urinary NTX/creatinine ratio (−57% vs. −46%, P < 0.001) and bone-specific alkaline phosphatase (−47% vs. −40%, P < 0.001). In the ALN/5600 group, by 12 months the increase in BMD was greater at the lumbar spine (4.9% vs. 3.9%, P = 0.047) and the total hip (2.2% vs. 1.4%, P = 0.035), significantly fewer patients were vitamin D—insufficient (11.3% vs. 36.9%, P < 0.001), and bone turnover marker (BTM) results were similar to those at 6 months. There was no difference between groups in those who experienced falls or fractures, and adverse events were similar. Based on the finding that ALN/D5600 was more effective than standard care at correcting vitamin D insufficiency, increasing BMD, and reducing BTMs in this patient group, greater attention needs to be directed toward optimizing the treatment of osteoporosis and correcting vitamin D deficiency in postmenopausal women.     

Genetic influences on bone loss in the San Antonio Family Osteoporosis study

Summary  The genetic contribution to age-related bone loss is not well understood. We estimated that genes accounted for 25–45% of variation in 5-year change in bone mineral density in men and women. An autosome-wide linkage scan yielded no significant evidence for chromosomal regions implicated in bone loss. Introduction  The contribution of genetics to acquisition of peak bone mass is well documented, but little is known about the influence of genes on subsequent bone loss with age. We therefore measured 5-year change in bone mineral density (BMD) in 300 Mexican Americans (>45 years of age) from the San Antonio Family Osteoporosis Study to identify genetic factors influencing bone loss. Methods  Annualized change in BMD was calculated from measurements taken 5.5 years apart. Heritability (h²) of BMD change was estimated using variance components methods and autosome-wide linkage analysis was carried out using 460 microsatellite markers at a mean 7.6 cM interval density. Results  Rate of BMD change was heritable at the forearm (h² = 0.31, p = 0.021), hip (h² = 0.44, p = 0.017), spine (h² = 0.42, p = 0.005), but not whole body (h² = 0.18, p = 0.123). Covariates associated with rapid bone loss (advanced age, baseline BMD, female sex, low baseline weight, postmenopausal status, and interim weight loss) accounted for 10% to 28% of trait variation. No significant evidence of linkage was observed at any skeletal site. Conclusions  This is one of the first studies to report significant heritability of BMD change for weight-bearing and non-weight-bearing bones in an unselected population and the first linkage scan for change in BMD.     

External hip protectors are effective for the elderly with higher-than-average risk factors for hip fractures

Summary  In our cluster randomised controlled trial for efficacy of hip protector with 672 ambulatory elderly women, a hip protector was more effective for prevention of hip fractures in residents with fall history (n = 202; hazard ratio (HR), 0.375; 95%CI, 0.14–0.98; p = 0.05) and body-mass index (BMI) ≤ 19.0 (n = 206; HR, 0.37; 95%CI, 0.14–0.95; p = 0.04) by a Cox proportional hazards regression model. Introduction  Hip fractures result from both osteoporosis and falling. A potentially cost-effective method of preventing hip fractures involves the use of hip protectors but recent studies have revealed the uncertain effectiveness of hip protectors even in institutional settings. Methods  This study was a cluster randomised controlled trial with nursing homes. We randomly assigned 76 homes with 672 ambulatory but frail elderly women. Several risk factors were assessed at baseline and incorporated into a Cox proportional hazards regression model. UMIN Clinical Trials Registry number is UMIN000000467. Research period was between January 2004 and March 2006. Results  In the intervention group, 19 hip fractures occurred (54.0/1,000 person-years), whereas 39 hip fractures occurred in the control group (78.8/1,000 person-years). Hazard ratio of hip fracture in the intervention group was 0.56 (95%CI, 0.31–1.03; p = 0.06) after adjusting for risk factors. In subgroup analysis, hip protectors were more effective for prevention of hip fractures in residents with fall history (n = 202; HR, 0.375; 95%CI, 0.14–0.98; p = 0.05) and BMI ≤ 19.0 (n = 206; HR, 0.37; 95%CI, 0.14–0.95; p = 0.04). Overall compliance with use of hip protectors was 79.7%. Conclusion  Risk of hip fracture can be reduced by hip protectors among elderly women with fall history and low BMI.     

Effects of a multi-component exercise program and calcium–vitamin-D3-fortified milk on bone mineral density in older men: a randomised controlled trial

Summary  We examined the independent and combined effects of a multi-component exercise program and calcium–vitamin-D₃-fortified milk on bone mineral density (BMD) in older men. Exercise resulted in a 1.8% net gain in femoral neck BMD, but additional calcium–vitamin D₃ did not enhance the response in this group of older well-nourished men. Introduction  This 12-month randomised controlled trial assessed whether calcium–vitamin-D₃-fortified milk could enhance the effects of a multi-component exercise program on BMD in older men. Methods  Men (n = 180) aged 50–79 years were randomised into: (1) exercise + fortified milk; (2) exercise; (3) fortified milk; or (4) controls. Exercise consisted of high intensity progressive resistance training with weight-bearing impact exercise. Men assigned to fortified milk consumed 400 mL/day of low fat milk providing an additional 1,000 mg/day calcium and 800 IU/day vitamin D₃. Femoral neck (FN), total hip, lumbar spine and trochanter BMD and body composition (DXA), muscle strength 25-hydroxyvitamin D and parathyroid hormone (PTH) were assessed. Results  There were no exercise-by-fortified milk interactions at any skeletal site. Exercise resulted in a 1.8% net gain in FN BMD relative to no-exercise (p < 0.001); lean mass (0.6 kg, p < 0.05) and muscle strength (20–52%, p < 0.001) also increased in response to exercise. For lumbar spine BMD, there was a net 1.4–1.5% increase in all treatment groups relative to controls (all p < 0.01). There were no main effects of fortified milk at any skeletal site. Conclusion  A multi-component community-based exercise program was effective for increasing FN BMD in older men, but additional calcium–vitamin D₃ did not enhance the osteogenic response.     

A Prospective Study of Bone Loss in Menopausal Australian-Born Women

Two hundred and twenty-four women (74 pre-, 90 peri-, 60 post-menopausal), aged 46–59 years, from a population-based cohort participated in a longitudinal study of bone mineral density (BMD). BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and femoral neck and the time between bone scans was on average 25 (range 14–41) months. The aim of the study was to assess changes in BMD in relation to changes in normal menopausal status. During the study period women who were between 3 and 12 months past their last menstrual period (n= 22, late perimenopausal) at the time of the second bone scan had a mean (SE) annual change in BMD of 70.9% (0.4%) at the lumbar spine and 70.7% (0.6%) at the femoral neck (both p50.05 compared with women who remained premenopausal). In the women who became postmenopausal (n= 42) the mean annual changes in BMD were 72.5% (0.2%) at the lumbar spine and 71.7% (0.2%) at the femoral neck (both p50.0005), and in the women who remained postmenopausal (n= 60) they were 70.7% (0.2%) per year and 70.5% (0.3%) per year respectively (both p50.05), compared with women who remained premenopausal. In the 1–3 years after the final menstrual period (FMP) there was greater bone loss from the lumbar spine than the femoral neck (p50.05). In women who were menstruating at the time of the second bone scan and whose FMP could be dated prospectively (n= 35), higher baseline oestradiol levels were associated with less lumbar spine bone loss (p50.005). In the women who remained postmenopausal there was an association between baseline body mass index (BMI) and percentage change per year in femoral neck BMD (p50.05), such that women with higher BMI had less bone loss. In conclusion, during the time of transition from peri- to post-menopause, women had accelerated BMD loss at both the hip and spine. Received: 23 June 1997 / Accepted: 5 November 1997